Results: As of 31 July 2015, 1 subject with severe SCD (Subject 1204, βS/βS with multiple vaso-occlusive crises, silent infarct, acute chest syndrome, and on prophylactic transfusions) and 3 subjects withβ-thalassemia major (Subjects 1201, 1202 and 1203) have been infused with the LentiGlobin BB305 Drug Product. The outcome of these subjects to date is shown in Table 1. No subject has experienced a drug product-related adverse event, and ISA analyses demonstrate highly polyclonal reconstitution without clonal dominance. The subject with severe SCD is producing approximately 51.5% of anti-sickling hemoglobin (48% HbAT87Q, 1.8% HbF, 1.7% HbA2) at 9 months post-infusion. This subject has not had a post-infusion hospitalization for a SCD-related event despite stopping chronic transfusions at Day +88. Both subjects with β0/βE-thalassemia major have remained transfusion-free for at least 15 months post-infusion, with a consistent expression of βA-T87Q-globin; the subject with β0/β0-thalassemia major has only had 1 month follow-up post-drug product infusion to date.

Conclusion: The subject with severe SCD is producing approximately 51.5% anti-sickling globins with HbS of 48.5% and remains free of SCD-related events despite stopping chronic transfusion therapy. Two subjects with β0/βE-thalassemia major remain transfusion-free for at least 15 months post infusion of LentiGlobin BB305 Drug Product. Gene therapy using autologous HSC transduced with LentiGlobin BB305 lentiviral vector is a promising approach for the treatment of patients with hemoglobinopathies.

Subject

Age (years)/ Sex (M/F)

Genotype

BB305 Drug Product

Day of Neutrophil Engraftment

Drug Product- related Adverse Events

Day of Last pRBC Transfusion

Last Study Visit (Months)

Hb at Last Visit (g/dL)

VCNa

CD34+ cell dose (x106 per kg)

Subject with severe sickle cell disease

HbAT87Q/HbF/ HbS/Total Hb

1204

13/ M

βS/βS

1.2 / 1.0

5.6

Day +37

None

Day +88

9M

5.5/0.2/5.5/11.4

Subjects with β-thalassemia major

Hb AT87Q/ Total Hb

1201

18/ F

β0/βE

1.5

8.9

Day +13

None

Day +10

18M

7.8/10.7

1202

16/ M

β0/βE

2.1

13.6

Day +15

None

Day +12

15M

9.7/12.8

1203

19/ M

β0/β0

0.8

8.8

Day +28

None

Day +15

1M

Pending/9.2

As of 31 July 2015

aVCN, vector copy number; F=female; M= Male for gender, and months for day of last follow-up